Barrett's esophagus predisposes to esophageal adenocarcinoma, the most rapidly increasing cancer in the United States. Unfortunately, esophageal adenocarcinoma is usually discovered when it is advanced and incurable, and 93% of patients will eventually die of their disease. Intensive endoscopic surveillance of patients with Barrett's esophagus can detect early and potentially curable cancers, but such surveillance is costly and time consuming. DNA Content flow cytometry can detect a subset of patients who have populations of cells with aneuploid or increased 4N fractions and who have an increased risk of progressing to cancer. DNA content flow cytometry cannot, however, distinguish those patients with aneuploidy or increased 4N fractions who will progress to cancer from those who will remain stable or even regress, nor can it identify the subset of patients who will develop aneuploidy or increased 4N fractions. There is, therefore, a need for intermediate biomarkers of neoplastic progression in Barrett's esophagus that can identify subsets of patients who: 1) are at low risk of progression to cancer and, therefore, do not require frequent endoscopic surveillance; 2) have an increased risk of progression to cancer and, therefore, require more frequent endoscopic surveillance; 3) have such a high risk of progression to cancer that esophagectomy is indicated even if cancer cannot be diagnosed preoperatively. Once these biomarker of neoplastic progression have been characterized, they could be used as intermediate endpoints for future dietary or medical intervention studies to prevent or reverse the abnormalities that lead to cancer in Barrett's esophagus. The long-term goal of this research is to develop intermediate biomarkers of neoplastic progression in Barrett's esophagus that can be used to improve the management of the cancer risk in this disease. Our research addresses two questions. First, what is the relationship between the development of allelic deletions of tumor suppressor genes and progression to cancer in Barrett's esophagus? Second, what is the relationship between the development of cell cycle abnormalities (increased G1 and S phase fractions) and progression to cancer in Barrett's esophagus?